Synthesis and Characterization of Andrographolide Derivatives as Regulators of βAPP Processing in Human Cells

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5′,7′-dichloro-8′-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2′-methyl-5′,7′-dichloro-8′-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as β-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting β-secretase that could prove useful in our quest for the therapeutic treatment of AD.     

1,3,5‐Triiodo‐2,4,6‐trimethylbenzene at 293 K

In the structure of tri­iodo­mesityl­ene (1,3,5‐tri­iodo‐2,4,6‐tri­methyl­benzene), C₉H₉I₃, at 293 K, the benzene ring is found to be significantly distorted from ideal D_6h symmetry; the average endocyclic angles facing the I atoms and the methyl groups are 123.8 (3) and 116.2 (3)°, respectively. The angle between the normal to the molecular plane and the normal to the (100) plane is 5.1°. No disorder was detected at 293 K. The thermal motion was investigated by a rigid‐body motion tensor analysis. Intra‐ and intermolecular contacts are described and topological differences compared with the isomorphous compounds tri­chloro­mesityl­ene and tri­bromo­mesityl­ene are discussed.     

Current Density‐Voltage and Capacitance‐Voltage Characteristics of Local p‐n Junction Structures in CuInSe2 Single Crystals

Local p‐n junction were obtained under room temperature conditions in CuInSe2 by applying strong electric field through small indium and copper contacts. The current density voltage (J‐V) and the capacitance‐voltage (C‐V) of three different samples were measured at room temperature. The J‐V method shows that the current is dominated by the drift component of the injected carriers. The C‐V method gave a barrier height of 1.04 eV for all three samples which agrees with the reported energy gap of this material. Analysis of these results indicate that the p‐n junction structures formed by strong electric fields are hihgly compensated and the current transport is dominated by the space charge limited current effect.     

Characterization of europium doped lanthanum oxide films prepared by spray pyrolysis

In this work the characterization of europium doped lanthanum oxide films prepared by ultrasonic spray pyrolysis is reported. The films were prepared from lanthanum and europium nitrates over a corning glass substrate. The films structure was analyzed by X-ray diffraction, Microscopy Electronic and energy dispersive spectroscopy analysis. Photoluminescence and Raman scattering were performed. The excitation spectrum consists of the charge transfer peak at 280 nm and several lines in the 350–450 nm range corresponding to f–f transitions. The emission spectrum, excited at 280 nm, shows five peaks at 580, 595, 615, 652 and 698 nm, corresponding to the transitions of trivalent europium ion. The optical properties of films were compared with the one obtained from powders prepared by precipitation and heating of the precursor material.     

The Stochastic Theory of Fluvial Landsurfaces

A stochastic theory of fluvial landsurfaces is developed for transport-limited erosion, using well-established models for the water and sediment fluxes. The mathematical models and analysis are developed showing that some aspects of landsurface evolution can be described by Markovian stochastic processes. The landsurfaces are described by nondeterministic stochastic processes, characterized by a statistical quantity, the variogram, that exhibits characteristic scalings. Thus the landsurfaces are shown to be self-organized critical (SOC) systems, possessing both an initial transient state and a stationary state, characterized by respectively temporal and spatial scalings. The mathematical theory of SOC systems is developed and used to identify three stochastic processes that shape the surface. The SOC theory of landsurfaces reproduces established numerical results and measurements from digital elevation models (DEMs).     

Variable selection in discriminant analysis based on the location model for mixed variables

Non-parametric smoothing of the location model is a potential basis for discriminating between groups of objects using mixtures of continuous and categorical variables simultaneously. However, it may lead to unreliable estimates of parameters when too many variables are involved. This paper proposes a method for performing variable selection on the basis of distance between groups as measured by smoothed Kullback–Leibler divergence. Searching strategies using forward, backward and stepwise selections are outlined, and corresponding stopping rules derived from asymptotic distributional results are proposed. Results from a Monte Carlo study demonstrate the feasibility of the method. Examples on real data show that the method is generally competitive with, and sometimes is better than, other existing classification methods.     

Growth of Quantum-Well Heterostructures by Liquid Phase Epitaxy

This work reviews the different techniques proposed and used to grow ultra-thin layers by Liquid Phase Epitaxy. Some of these approaches have allowed the production of quantum-well heterostructures for optoelectronic devices with performances comparable to devices made by Molecular Beam Epitaxy or Metal Organic Chemical Vapor Deposition.     

Are CP Violating Effects in the Standard Model Really Tiny?

We derive an effective action of the bosonic sector of the Standard Model by integrating out the fermionic degrees of freedom in the worldline approach. The CP violation due to the complex phase in the CKM matrix gives rise to CP-violating operators in the effective action. We calculate the prefactor of the appropriate next-to-leading order operators and give general estimates of CP violation in the bosonic sector of the Standard Model. In particular, we show that the effective CP violation for weak gauge fields is not suppressed by the Yukawa couplings of the light quarks and is much larger than the bound given by the Jarlskog determinant.